4

Multi-drug resistant
tuberculosis in Russia. Lessons from a cholera epidemic. Feline immunodeficiency
virus. Leaf-cutter ants and symbiosis. Allergies and the importance
of interactions among species.

A. Microbes as Predators

"The Cold War is
history," the narrator begins, "but Russia is in the grip
of an arms race--an evolutionary arms race, with an enemy the naked
eye cannot see." After some scenes of predators catching their
prey, and bacteria multiplying under a microscope, we find ourselves
in a room crowded with prison inmates--some of them coughing. "A
deadly microbe is evolving in Russia's prisons," the narrator
continues ominously, "consuming the bodies of men. As it escapes
prison walls, it attacks new prey, without preference, without warning."
Suddenly we are transported to New York City. "Now the killer
is spreading beyond Russia, and no one is immune. Unseen, the microbe
is evolving into mutants that may soon elude our best defenses.
Will we lose this arms race, or can we reach an evolutionary truce
with a mortal enemy?"

The scene switches to
western Oregon, "home to one of evolution's most extreme and
deadly creations"--a species of newt that defends itself from
predatory snakes with tetrodotoxin, a potent nerve poison. Each
newt produces enough toxin to kill scores of other animals, but
why so much? Research shows that the garter snakes that prey on
them have a certain amount of resistance to the toxin. A newt that
produces slightly more toxin than its neighbors might overcome the
snakes' resistance and survive. If its offspring inherit the ability
to produce more toxin, subsequent generations might evolve higher
toxin levels. The snakes, in like manner, might evolve higher levels
of resistance, and the result would be an "evolutionary arms
race" between the two species.

Evolution, we are told,
is driven not just by physical forces such as climatic change, but
even more by biological forces--the ways species interact with each
other. As we watch some more wildlife photography, the narrator
asks: "What made the lion fast, and the zebra fierce? What
drove the development of tooth and claw? The deadly dance of predator
and prey has shaped the evolution of countless species. There may
have been a time on an ancient savanna when hungry beasts hunted
our ancestors, and drove the evolution of our own species."

We find ourselves once
again on crowded city streets, as the narrator continues: "But
since the dawn of civilization, only one kind of predator has truly
threatened us. The microorganisms that cause disease consume us
from the inside out." They also reproduce much faster than
we do--a fact dramatized by time-lapse microphotography. "By
evolving much faster than we do, microbes have eluded the body's
defenses, and left their mark on our history."

The bacteria that cause
tuberculosis have been detected in Egyptian mummies, and have preyed
on people for thousands of years. A different microbe caused the
"Black Death" in the fourteenth century, which killed
a third of all Europeans. And still another caused the 1918 flu
epidemic, which claimed 20 million lives. "We were virtually
defenseless against these microscopic killers until recently,"
the narrator says. An old newsreel shows a hospital--"a battlefield
in man's total war against disease"--and calls antibiotics
"the miracle drugs of our time." Antibiotics initially
seemed to be so successful that by 1969 the U. S. Surgeon General
thought the war on infectious disease had been won. But he spoke
too soon.

B. Drug-resistant Tuberculosis

We return to Russia,
to the room crowded with prison inmates. Since the fall of the Soviet
Union, the narrator says, Russia's prison population has soared.
"But overcrowding, poor nutrition, and scant sanitation are
not the worst of the prisoners' worries. Now tuberculosis stalks
these men." Microbes that might lie dormant in otherwise healthy
people erupt into active disease in these men, because their immune
systems have been weakened by unhealthy lifestyles and prison over-crowding.

Many of these victims
were previously treated for tuberculosis (TB), but their treatment
was not continued long enough to cure them completely. Describing
one such victim, the narrator says: "Evolution has occurred
inside his body." When he was first diagnosed with TB, he was
given drugs that killed some bacteria but spared "the ones
with mutations that made them resistant to the drugs. As these survivors
multiplied, they passed along their protective mutations to all
their descendants. In this way, the bacteria evolved into a new
drug-resistant strain."

In fact, he and more
than 30,000 other Russian prison inmates have TB that is resistant
to more than one drug. Although there are now new antibiotics to
treat strains with multi-drug resistance, they are expensive and
hard to get. When the prisoners are released, they can spread these
resistant strains to the general population--and thus to the rest
of the world, including the U.S.

Doctors and nurses scurry
around an emergency room to dramatize the possible consequences
of a TB epidemic in a U.S. city. The scene is frightening. "And
TB is just the tip of the iceberg," says the narrator. "The
microbes that cause malaria, pneumonia, gonorrhea, and scores of
other infectious diseases are evolving drug resistance."

"We've created this
problem," a researcher tells us. "Multi-drug resistance
is a man-made problem." This is because antibiotics are being
used too much. "By developing as many antibiotics as we have
over the last fifty years, we've essentially accelerated an evolutionary
process. The outcome is that we're going to have
more drug-resistant microbes--to the point where some of the
most dangerous bacteria will not be treatable. We're racing against
the microbe every day, and unfortunately we're losing."See
. Multi-drug-resistant TB is an important public health problem.
For more information, go to:

There may be a solution,
however. "In an arms race without end, the more drugs we launch
at microbes the more resistance they evolve," the narrator
says. "It may be time to change our strategy, and make evolution
work for us."

C. Can Cholera Be Domesticated?

The camera pans over
a tree-covered college campus, and the narrator continues: "If
we can make microbes more resistant, then we can also make them
less harmful to us--less virulent."

Amherst College evolutionary
biologist Paul Ewald explains: "When people are looking at
the antibiotic resistance problem, they see evolution as sort of
the bad guy. It's the evolutionary process that's led to antibiotic
resistance--and that's true. But just as easily, we can have evolution
being the solution. In other words, we can have evolutionary processes
leading to organisms becoming more mild."

According to Ewald, microbes
that are transmitted through direct person-to-person contact--such
as cold viruses--tend to be mild, because they require basically
healthy people for their transmission. But microbes that are transmitted
through insects, food, or water--such as cholera--tend to make people
very sick. "Once we understand the factors that favor increased
harmfulness and decreased harmfulness," Ewald reasons, "then
we can look at all of the things we do in society. We can ask the
question, `Are we doing certain things, or can we do certain things,
that would favor organisms evolving towards mildness.'"

Ewald studied a 1991
cholera outbreak in South America that sickened over a million people
and killed almost 11,000, in order to "document evolution in
action." Ewald explains: "If you have contaminated water
allowing transmission, we expect the cholera organism to evolve
to a particularly high level of harmfulness. And that's exactly
what we see. We find that bacteria that had invaded countries with
poor water supplies evolved increased harmfulness over time."

"If, instead, we
clean up the water supplies," Ewald continues, "then we
force the bacteria to be transmitted only by routes that require
healthy people. And what we find is that when cholera invaded countries
with clean water supplies, the organism dropped in its harmfulness.
Those bacteria evolved [a] lower level of toxin production--they
actually became more mild through time.

"People would still
be getting infected, but the infections would be so mild that most
people wouldn't even be sick. So the cholera outbreak in Latin America
suggests that we may need only a few years to change the cholera
organism from one that would often kill people to one that hardly
ever causes the disease. What we're suggesting here is that we can
domesticate these disease organisms."

But there are serious
problems with Ewald's story. First, he claims that microbes spread
through person-to-person contact tend to be less harmful than those
spread by insects, food and water. But TB--the harmfulness of which
was just impressed on us--spreads through person-to-person contact.
So did the 1918 flu, which killed more people in less time than
the infamous Black Death. Since cholera is transmitted through water
or food--not through person-to-person contact--regardless of whether
it is mild or harmful, Ewald's hypothesis is wrong from the start.

The lesson to be learned
from this is that our first lines of defense against infectious
diseases are to keep our food and water clean, and to maintain our
general health by eating nutritious foods. Although no one who has
ever needed antibiotics will dispute their usefulness, their contribution
to public health is minor compared to improved sanitation and nutrition.

So if you don't want
to die of cholera, drink clean water and eat clean, nutritious food.
Evolution has nothing to do with it.

Like all other infectious
diseases, TB declined dramatically in England before the advent
of modern medicine, and for the same reasons. As we were told a
few minutes ago, Russian prison inmates develop active TB because
their immune systems have been weakened by unhealthy lifestyles
and poor nutrition. Add overcrowding and poor sanitation, and illness
is to be expected. Of course, the problem of multi-drug resistance
cannot be ignored; but once again, general sanitation and nutrition
turn out to be far more important than evolutionary considerations.

In any case, evolution
in cholera virulence and TB antibiotic resistance involves only
changes within existing species--just as we saw in the case of HIV.
The TB we battle today is the same species as the TB found in Egyptian
mummies.

We didn't need Darwin
to teach us about minor changes within existing species; in the
form of domestic breeding, such changes have been understood and
used for centuries. True, Darwin realized that a similar selection
process operates in the wild. But where is the evidence for his
theory that this process explains the origin of
new species--in fact, of every species?

D. Feline Immunodeficiency
Virus

We leave the Amherst
College campus and go to the National Zoo in Washington, DC, as
the narrator says: "Peaceful co-existence with disease organisms
may seem like a revolutionary idea. But throughout evolution, other
species have also reached a truce with these microscopic killers."

Geneticist Stephen J.
O'Brien describes his study of feline immunodeficiency virus (FIV),
which is associated with an immune-deficiency disease in domestic
cats. He examined DNA from every species of cat--from cheetahs to
ocelots, and lynxes to lions--and concluded that "virtually
every species of cats on the planet had been exposed to and infected
with a version of feline immunodeficiency virus." But no species
of wild cats suffer from immune-deficiency disease. Apparently,
they are immune to the effects of FIV.

Applying evolutionary
thinking, O'Brien speculates that FIV first infected the cats' ancestors
three to six million years ago. The narrator describes the supposed
consequences: "It decimated the animals. But a lucky few were
born with mutations that happened to make them immune to the virus.
These survivors passed on their protective genes to most cat species
alive today. Domestic cats are a young species, and a recent conquest
for FIV. But wild cats have reached the end of a long phase of adapting
to a once-deadly foe."

"Sadly," the
narrator continues, "we have just begun such a phase with a
close relative of FIV--the human immunodeficiency virus. But the
example of the cats convinced O'Brien that some people must be endowed
with genetic mutations that make them immune to HIV. He set out
to find them." And O'Brien found a mutation that he concluded
helps protect some people from HIV infection. Applying evolutionary
thinking again, O'Brien speculates that this mutation may also have
protected Europeans from the Black Death in the fourteenth century.

There are problems with
the FIV story, however. First, if all modern members of the cat
family inherited a mutation from their common ancestor that protects
them from the effects of FIV infection, and domestic cats are the
youngest members of the family, then why didn't they inherit the
mutation, too? Perhaps the immunity of wild cats is not due to a
mutation at all, and it is the environment of domestic cats that
renders them susceptible to disease. But this possibility is not
even mentioned.

Second, and more importantly,
nothing in this story helps us to understand how FIV or HIV--much
less cats or humans--evolved. As we have already seen, changes in
an existing species are a far cry from the origin of a new species.
Even if everything we have just been told about FIV and HIV were
true, it would not provide evidence that "leopards and lichens,
minnows and whales, flowering plants and flatworms, apes and human
beings" evolved from a common ancestor through natural selection
and random variation, as Darwin's theory implies.

Third, nothing in this
story shows that an understanding of evolution is necessary to medical
research. O'Brien's speculations about the evolutionary history
of FIV have done nothing to cure domestic cats of their disease.
And his finding that some people have a mutation that supposedly
protects them from AIDS has done nothing for the victims of that
disease. The producers of Evolution claim that evolution "touches
our daily lives in extraordinary ways," especially when it
comes to medicine. Yet this story shows nothing like that.

E. Symbiosis and Leaf-Cutter
Ants

"But evolution arises
not just from conflict and competition," the narrator says,
"the history of life is also the story of different species
joining forces."

There is another force,
we are told, that is just as important as competition in building
up "the magnificent super-structure" of the world of living
things, and that is "cooperation--what we call symbiosis, and
particularly mutualistic symbiosis. That is intimate living-together
of different kinds of organisms, in which there is a partnership
which benefits both of the partners."

After being shown several
examples of this, we are introduced to leaf-cutter ants in the Amazonian
jungle. These ants are like gardeners--they harvest leaves that
they chew into a pulp, then they use the pulp to grow a fungus that
supplies them with sugar. This is mutualistic symbiosis: The fungus
depends on the pulp provided by the ants, and the ants depend on
the sugar produced by the fungus.

Remarkably, the ant's
"gardens" are pest-free, unlike human gardens. It turns
out that the many of the ant-gardeners are covered with a white,
waxy coating of Streptomyces bacteria. Streptomyces--the source
of medically useful antibiotics such as streptomycin--keeps in check
an aggressive mold that would otherwise devastate the cultivated
fungus.

"The ants have been
using antibiotics to kill the mold in their gardens for some fifty
million years," says the narrator, "so why hasn't the
mold evolved antibiotic resistance?" The answer, we are told,
is that the Streptomyces bacteria covering the ants is probably
evolving along with the aggressive mold that it keeps in check.
The result is supposedly "an evolutionary arms race that has
continued for fifty million years"--though we are not shown
any evidence for this at all.

So leaf-cutter ants provide
us with an excellent example of mutualistic symbiosis, and may also
provide us with another example of an evolutionary arms race. This
is a fascinating story. But what does it have to do with Darwinian
evolution? We have seen that several species can co-exist in a symbiotic
relationship. But we have not seen evidence for how that relationship
developed, much less for how the species originated in the first
place.

F. Microbes Can Be
Good For Us

Microbes are an important
part of our world, we are told, yet we seem to do everything in
our power to avoid contact with them. "Is it possible we're
making our world too clean?" asks
the narrator.

We visit a German pediatrician
who treats allergies and asthma--"disorders in which the immune
system overreacts to harmless substances," explains the narrator.
Research conducted by the pediatrician suggests that children who
live in villages suffer more from such disorders than children who
live on nearby farms. She finds that children who come into regular
contact with livestock are less likely to develop allergies and
asthma.

The pediatrician suspects
that high levels of microorganisms in the stables help children
to form healthier immune systems. "Microbes have been around
us always," she concludes, "and probably we need to find
the balance between eradicating the harmful effect of bacteria,
and maybe also taking the beneficial components of this."

So we need to drink clean
water, and eat clean food; but perhaps we don't want our environment
to be too clean.

As the episode closes,
we are told that it's a big mistake to separate ourselves too much
from the rest of living things. After all, most species are our
friends rather than our enemies. In fact they are essential to our
existence, and we would do well to learn more about them. Surely,
these are wise words. But do we really need to understand Darwinian
evolution in order to appreciate them?

In fact, most of what
we've heard in this episode would have made just as much sense if
the word "evolution" hadn't been used at all. True, we
can use the word to explain why newts make an excessive amount of
poison; but we haven't thereby explained how newts acquired the
ability to make the poison, much less how newts originated in the
first place. Minor changes within species have been known for centuries.
What we need to see is evidence that the same process can produce
the big changes required by Darwin's theory, but that evidence has
not been forthcoming.

Nor does this episode
show that we need to understand evolution in order to practice good
medicine. True, we can use the word to describe how TB becomes resistant
to antibiotics; but it's still the same TB we find in Egyptian mummies,
and a healthy lifestyle may still be the best defense against it.
Cholera epidemics can be prevented without knowing anything at all
about evolution, and studying FIV evolution has done nothing to
help AIDS sufferers.

Clearly, the "evolutionary
arms race" metaphor is not the only way--and may not even be
the best way--to understand our relationship to bacteria. Although
this episode started with ominous warnings of a microbial holocaust,
it ends with the comforting assurance that most microbes are our
friends. Darwinism seems to explain everything and its opposite
equally well. But if competition and cooperation are equally compatible
with evolution, what difference does Darwinism really make?

Notes

.
Multi-drug-resistant TB is an important public health problem.
For more information, go to:

http://www.biomedcentral.com/news/20010402/05
or

http://www.who.int/gtb/publications/dritw/index.htm
or

http://www.hopkins-tb.org/news/

.
For more information on Ewald's hypothesis, see Paul W. Ewald,
Evolution of Infectious Diseases (Oxford: Oxford University Press,
1996). For more information about cholera, go to:

http://www.bact.wisc.edu/Bact330/lecturecholera
or

http://vm.cfsan.fda.gov/~MOW/chap7.html

The decline
in infectious diseases (including TB) from the seventeenth century
to the nineteenth largely preceded the advent of modern medicine,
and was due to general improvements in sanitation and nutrition.
See Thomas McKeown, The Role of Medicine (Princeton: Princeton University
Press, 1979).

.
Alan H. Linton is emeritus professor of bacteriology at the University
of Bristol (U.K.). The quotation is from The Times Higher Education
Supplement (April 20, 2001), 29.

The person
who has probably come closer than anyone to producing new species
of bacteria is Michigan State University biologist Richard E. Lenski.
But Lenski has only been able to produce "an incipient genetic
barrier between formerly identical lines"--a barrier which
he admits is "much smaller than the barrier between such clearly
distinct species as E. coli and Salmonella enterica." See Martin
Vulic, Richard E. Lenski, and Miroslav Radman, "Mutation, recombination,
and incipient speciation of bacteria in the laboratory," Proceedings
of the National Academy of Sciences USA 96 (1999), 7348-7351.